This paper belongs to a series of three publications that examine the intestinal barrier, its role in health and disease and the potential impact of probiotics on function. In this review, the authors describe the role of different mechanisms and interactions that support the maintenance of intestinal barrier function. The authors also discuss biomarkers in blood, feces, or urine that can be used to assess intestinal permeability and epithelial integrity.

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of sIgA and antimicrobial peptides and proteins. With exception of sIgA the expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of gastrointestinal disorders. Additionally, the gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the HPA-axis and both mast cell-dependent as well as mast cell- independent mechanisms. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in patients but there remains a need to explore their use in assessing impact of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of the available biomarkers and their predictive value for gut health in human cohorts.